AB0129 EXPLORING LONG NON-CODING RNA GAS5 IN SLE PATIENTS AND ITS RELATION TO INTERFERON SIGNATURE
Authors: G. Maghraby, M. Elmeniawy, H. Mostafa, O. Shaker, M. Habib, R. Elgohary
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease with diverse pathogenesis. Excessive apoptosis and impaired clearance of apoptotic cells are the primary drivers of Interferon I (IFN) signaling pathways. Upregulation of the long noncoding RNA Growth arrest-specific 5 (GAS5) was found to be associated with apoptosis [1]. Oncological studies discovered that GAS5 is regulated by IFN signaling pathways and acts as a positive feedback loop on IFN response [2,3]. In a mouse model, GAS5 was linked to SLE susceptibility [4]. However, the exact mechanism is still unknown. Furthermore, GAS5 has been proposed to act by interfering with glucocorticoid action, with a key role in regulating glucocorticoid resistance and sensitivity [5]. <h3>Objectives</h3> To evaluate the expression levels of GAS5 in serum of SLE patients in comparison with healthy controls, assess their relation to SLE Disease Activity Index 2000 (SLEDAI-2K) and Systemic Lupus International Collaborating Clinics/ American College of Rheumatology Damage Index (SDI), and explore their association with each of the 3 IFN stimulatory genes (MX1, IFI44L, IFIT1) as well as IFN signature to elucidate how GAS5 shares in the pathogenesis of SLE. <h3>Methods</h3> 30 adult SLE patients and 20 age and sex-matched healthy controls were enrolled. SLE disease activity and damage were assessed by SLEDAI-2K and SDI respectively. The expression levels of GAS5 as well as 3 IFN stimulatory genes (MX1, IFI44L, IFIT1) were measured by quantitative real-time PCR. IFN signature score was calculated as described in a previous study [6]. <h3>Results</h3> GAS5 expression levels were insignificantly upregulated in SLE patients compared to control (p-value 0.11). At cut-off value 1.3-fold change, GAS5 could discriminate SLE from control (AUC 0.63) with high specificity 100 % and modest sensitivity 63%. Their expression levels were not associated with SLEDAI-2K or SDI scores. GAS5 levels were positively correlated with the cumulative dose of steroids in the last 6 months. However, it was not statistically significant. GAS5 was significantly correlated with IFIT1 gene expression (p-value &lt;0.001) and IFN signature score (p-value 0.005) in SLE patients (Figure1), these findings were not previously reported. <h3>Conclusion</h3> GAS5 may be considered a diagnostic biomarker for SLE, but it is not a reliable biomarker for disease activity or damage. GAS5 is suggested to be incorporated into the IFN signaling pathway in SLE raising possible contribution in SLE pathogenesis. <h3>References</h3> [1] Kino et al. Noncoding RNA gas5 is a growth arrest–and starvation-associated repressor of the glucocorticoid receptor. Science signaling. 2010. [2] Huang et al. Long non-coding RNA GAS 5 is induced by interferons and plays an antitumor role in esophageal squamous cell carcinoma. Cancer medicine. 2018. [3] Xu et al. Long noncoding RNA GAS5 inhibits proliferation and metastasis in papillary thyroid carcinoma through the IFN/STAT1 signaling pathway. Pathology-Research and Practice. 2022. [4] Haywood et al. Overlapping BXSB congenic intervals, in combination with microarray gene expression, reveal novel lupus candidate genes. Genes &amp; Immunity. 2006. [5] Lucafo et al. Long noncoding RNA GAS5: a novel marker involved in glucocorticoid response. Current molecular medicine. 2015. [6] Feng et al. Association of increased interferon-inducible gene expression with disease activity and lupus nephritis in patients with systemic lupus erythematosus. Arthritis &amp; Rheumatism. 2006. <h3>Acknowledgements</h3> We would want to express our gratitude to everyone who took part in this study, both SLE patients, and healthy control individuals. This study was funded by Cairo University. <h3>Disclosure of Interests</h3> None Declared.